Tumor suppressor let-7a inhibits breast cancer cell proliferation, migration and invasion by targeting MAGE-A1

Mi, Yanfang; Liu, F.; Liang, Xufei; Liu, S. N.; Huang, Xiao; Sang, Meixiang; Geng, Cheng

doi:10.4149/neo_2018_180302n146

Cited by 17 publications

(11 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been validated as RG in lymph node tissues 57 . Notably, let-7a is downregulated in breast cancer, prostate cancer, cervical cancer [58][59][60][61] … So far, there is no evidence in the literature of the implication of miR-191-5p, miR-34b-3p and let-7a-5p in the physiology of MSCs. To validate the selected RGs, the relative expression of miR-21-5p was measured by RT-qPCR.…”

Section: Discussionmentioning

confidence: 99%

The crucial choice of reference genes: identification of miR-191-5p for normalization of miRNAs expression in bone marrow mesenchymal stromal cell and HS27a/HS5 cell lines

Coste

Rouleux‐Bonnin

2020

Sci Rep

View full text Add to dashboard Cite

Bone marrow mesenchymal stromal cells (BM-MSCs) have a critical role in tissue regeneration and in the hematopoietic niche due to their differentiation and self-renewal capacities. These mechanisms are finely tuned partly by small non-coding microRNA implicated in post-transcriptional regulation. The easiest way to quantify them is RT-qPCR followed by normalization on validated reference genes (RGs). This study identified appropriate RG for normalization of miRNA expression in BM-MSCs and HS27a and HS5 cell lines in various conditions including normoxia, hypoxia, co-culture, as model for the hematopoietic niche and after induced differentiation as model for regenerative medicine. Six candidates, namely miR-16-5p, miR-34b-3p, miR-103a-3p, miR-191-5p, let-7a-5p and RNU6A were selected and their expression verified by RT-qPCR. Next, a ranking on stability of the RG candidates were performed with two algorithms geNorm and RefFinder and the optimal number of RGs needed to normalize was determined. Our results indicate miR-191-5p as the most stable miRNA in all conditions but also that RNU6a, usually used as RG is the less stable gene. This study demonstrates the interest of rigorously evaluating candidate miRNAs as reference genes and the importance of the normalization process to study the expression of miRNAs in BM-MSCs or derived cell lines.

show abstract

Section: Discussionmentioning

confidence: 99%

The crucial choice of reference genes: identification of miR-191-5p for normalization of miRNAs expression in bone marrow mesenchymal stromal cell and HS27a/HS5 cell lines

Coste

Rouleux‐Bonnin

2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…It has been reported that MAGE-A gene products are involved in ubiquitination, proliferation, and apoptosis [31,41,[53][54][55]. The relationship between MAGE-A proteins and ubiquitination is well known; for example, MAGEA3 and MAGEA6 form an E3 ubiquitin ligase complex with TRIM28, which participates in the survival of cancer cells by degrading AMPKa1 [31,55].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness

Kim

et al. 2021

Cancers

View full text Add to dashboard Cite

After decades-long efforts to diagnose and treat breast cancer, the management strategy that has proved most successful to date is molecular-subtype-specific inhibition of the hormone receptors and HER2 that are expressed by individual cancers. Melanoma-associated antigen (MAGE) proteins comprise >40 highly conserved members that contain the MAGE homology domain. They are often overexpressed in multiple cancers and contribute to cancer progression and metastasis. However, it remains unclear whether the biological activity arising from MAGE gene expression is associated with breast cancer subtypes. In this study, we analyzed the RNA-sequencing (RNA-seq) data of 70 breast cancer cell lines and found that MAGEA12 and MAGEA3 were highly expressed in a subset of these lines. Significantly, MAGEA12 and MAGEA3 expression levels were independent of hormone receptor expression levels but were closely associated with markers of active histone modifications. This indicates that overexpression of these genes is attributable to epigenetic deregulation. RNA-seq of MAGEA12-depleted cells was then used to identify 382 candidate targets of MAGEA12 that were downregulated by MAGEA12 depletion. Furthermore, our gain-of-function experiments showed that MAGEA12 overexpression promoted aggressive behaviors of malignant breast cancer cells, including enhancing their cell migration and invasion. These changes were associated with increased epigenetic deregulation of the MAGEA12 signature genes. Thus, MAGEA12 may play an important role in breast cancer malignancy. Taken together, our findings suggest that MAGEA12 could be a promising therapeutic target in breast cancer, and its overexpression and epigenetic changes could serve as subtype classification biomarkers.

show abstract

“…Intriguingly, both Let-7a and miR-26a were found downregulated in several human cancer types, acting as tumor-suppressor miRNAs [36][37][38][39][40]. Moreover, these miRNAs inhibited cell proliferation and invasiveness of malignant melanoma derived-cell lines, suggesting that miR-26a and Let-7a may represent novel therapies for melanoma [41].…”

Section: Discussionmentioning

confidence: 99%

HMGA1-Regulating microRNAs Let-7a and miR-26a are Downregulated in Human Seminomas

Martino

Esposito

Pellecchia

et al. 2020

IJMS

View full text Add to dashboard Cite

Background: Recent studies have underlined HMGA protein’s key role in the onset of testicular germ cell tumors, where HMGA1 is differently expressed with respect to the state of differentiation, suggesting its fine regulation as master regulator in testicular tumorigenesis. Several studies have highlighted that the HMGA1 transcript is strictly regulated by a set of inhibitory microRNAs. Thus, the aim of this study is to test whether HMGA1 overexpression in human seminomas may be induced by the deregulation of miR-26a and Let-7a—two HMGA1-targeting microRNAs. Methods: HMGA1 mRNA and Let-7a and miR-26a levels were measured in a seminoma dataset available in the Cancer Genome Atlas database and confirmed in a subset of seminomas by qRT-PCR and western blot. A TCam-2 seminoma cell line was then transfected with Let-7a and miR-26a and tested for proliferation and motility abilities. Results: an inverse correlation was found between the expression of miR-26a and Let-7a and HMGA1 expression levels in seminomas samples, suggesting a critical role of these microRNAs in HMGA1 levels regulation. Accordingly, functional studies showed that miR-26a and Let-7a inhibited the proliferation, migration and invasion capabilities of the human seminoma derived cell line TCam-2. Conclusions: these data strongly support that the upregulation of HMGA1 levels occurring in seminoma is—at least in part—due to the downregulation of HMGA1-targeting microRNAs.

show abstract

Tumor suppressor let-7a inhibits breast cancer cell proliferation, migration and invasion by targeting MAGE-A1

Cited by 17 publications

References 28 publications

The crucial choice of reference genes: identification of miR-191-5p for normalization of miRNAs expression in bone marrow mesenchymal stromal cell and HS27a/HS5 cell lines

The crucial choice of reference genes: identification of miR-191-5p for normalization of miRNAs expression in bone marrow mesenchymal stromal cell and HS27a/HS5 cell lines

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness

HMGA1-Regulating microRNAs Let-7a and miR-26a are Downregulated in Human Seminomas

Contact Info

Product

Resources

About